After stroke or other injuries to cortical motor areas, deficits include impaired motor planning and obligatory use of motor synergies with a loss of the ability to execute isolated movements at individual joints. The primary motor cortex (M1) and premotor areas like the supplementary motor area (SMA), the dorsolateral premotor cortex (PMd), and the post-arcuate premotor area (APA) are implicated to varying extents in motor planning and control over isolated movements. These cortical motor areas project to many different parts of the nervous system, but all project to the medial pontomedullary reticular formation (mPMRF). Neural activity in the mPMRF, however, has never been described during skilled arm movements in primates. As a first step in understanding the functions of the mPMRF, the proposed studies will employ motor tasks designed to differentially activate cortical centers that project to the mPMRF. In the premotor cortical areas, set-related neural activity often commences after an instruction specifies the upcoming movement and persists as movement is withheld during a waiting period. Experiment l will test for the presence of set- and movement-related activity in mPMRF neurons and will specifically identify mPMRF cells with inputs from cortex and/or outputs to spinal cord. Experiment 2 will determine which aspects of set- and movement-related mPMRF activity depend on cortical input by reducing cortical influence with muscimol microinjections into cortical motor areas. Cortical motor areas are also important for the control of isolated, single-joint movements, while the mPMRF, the source of the reticulospinal tracts, engages synergistic, multi-joint movements. Many corticospinal neurons emanating from rostral M1 and premotor areas send collaterals to the mPMRF that may coordinate corticoreticular and corticospinal activity to control movements in and out of synergy. By recording the activity of mPMRF neurons during reaching in and out of synergy specifically identifying mPMRF neurons receiving from cortical motor areas and/or projecting to spinal cord, experiment 3 will meet the third aim, to explore the role of the reticular formation and the cerebral cortex in coordinating motor synergies with isolated control. These experiments will elucidate cortical and subcortical coordination for the neural control of goal-directed reaching, leading to better rehabilitation after brain injury.